Chronic Obstructive Lung Disease, Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
To evaluate the regenerative capacities of mesenchymal cells composing the microenvironment of alveolar type 2 cells in a population of patients, undergoing thoracic surgery for suspected cancer, who are smokers with and without COPD compared to non-smokers patients
Detailed description
Chronic obstructive pulmonary diseases (COPD) have a major public health impact, as evidenced by the 250 million patients affected by these diseases and the 50% 5-year mortality for severe stages of chronic obstructive pulmonary disease (COPD). One pathophysiological mechanism of COPD and emphysema is a depletion of alveolar progenitor cells inducing a loss of alveolar-reparation capacities after an aggression. The genesis of these alterations and the mechanisms involved remain unknown. Alveolar type 2 cells (AT2) are the alveolar epithelial progenitor cells. AT2 proliferate and differentiate into alveolar type 1 cells (AT1) which form the alveolar-capillary barrier, along with endothelial cells, through which respiratory gas exchanges take place. The proliferation and differentiation of AT2 into AT1 are under the control of mesenchymal cells and endothelial cells located in close proximity. Together these cells form the alveolar stem cell niche. The characteristics and interactions of the different cell populations have been well described during lung growth, in the normal adult lung or during pulmonary fibrosis; however, participants are poorly described during smoking exposure and chronic obstructive diseases.
Interventions
OTHERThoracic resection surgery
Patients undergoing thoracic resection surgery (pneumonectomy, lobectomy, segmentectomy) for cancer or suspected cancer, including smokers (active or ex-smokers) and non-smokers, with COPD and without COPD, and non-smoking patients.
Sponsors
Henri Mondor University Hospital
Institut National de la Santé Et de la Recherche Médicale, France
Centre Hospitalier Intercommunal Creteil
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 2. Patient undergoing lung resection surgery (lobectomy, pneumonectomy, segmentectomy) for cancer or suspected cancer 3. Acceptance to participate in the protocol 4. Affiliated to a social security plan
Exclusion criteria
1. Chronic autoimmune disease 2. Patient under guardianship or curators 3. Neo-adjuvant chemotherapy 4. History of thoracic radiotherapy 5. Pregnant woman 6. Minor patient 7. Person not able to consent 8. Person deprived of liberty
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of alveolar organoids | through study completion, an average of 3 years | Comparison of the number of alveolar organoids formed 21 days after culture of fibroblasts with alveolar type II cells between smokers with and without COPD and non-smoking patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differentiation into myofibroblasts | through study completion, an average of 3 years | By immunofluorescence marking: number of alpha-smooth muscle actin (alpha-SMA) + cells compared to total cells |
| Fibroblast migration capacity | through study completion, an average of 3 years | Evaluated in Boyden chamber |
| Modulated signaling pathways in isolated fibroblasts between groups | through study completion, an average of 3 years | Evaluated by Ribonucleic acid (RNA) sequencing of fibroblasts |
| Modulated signaling pathways in endothelial cells between groups | through study completion, an average of 3 years | Evaluated byRibonucleic acid (RNA) sequencing of endothelial cells |
| Evaluation of cytokines in fibroblasts supernatant | through study completion, an average of 3 years | Evaluated by Luminex Assay |
| Tumor progression | through study completion, an average of 3 years | By studying the migration and invasion of tumor cells |
| Identification of different cell types on total lung | through study completion, an average of 3 years | Cell types composing the lung stem cell microenvironment measured by single cell analysis |
| Severity of pulmonary emphysema, | At inclusion, every year, up to 5 years after surgery | Change of lung density assessed by computed tomography scan |
| Fibroblast proliferation capacity | through study completion, an average of 3 years | Evaluated by their doubling time, number of cells collected compared to the number of cells seeded |
| Research of pulmonary biomarkers | through study completion, an average of 3 years | Searched according to the results obtained during cell cultures (immunohistochemistry, immunofluorescence) |
| Identification of biomarkers in the pre and postoperative circulating blood | through study completion, an average of 3 years | Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers |
| Identification of biomarkers in the intestinal microbiota | through study completion, an average of 3 years | Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers |
| Measurement of Forced expiratory volume at one second (FEV1) | through study completion, an average of 3 years | Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced expiratory volume at one second (FEV1) |
| Measurement of Forced Vital Capacity (FVC ) | through study completion, an average of 3 years | Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced Vital Capacity (FVC ) |
| Measurement of pulmonary diffusion capacity of CO (DLCO) | through study completion, an average of 3 years | Determine the relationship between respiratory disease phenotype and exercise impact by measurement of pulmonary diffusion capacity of CO (DLCO) |
| Measurement of CO transfer coefficient (KCO) | through study completion, an average of 3 years | Determine the relationship between respiratory disease phenotype and exercise impact by measurement of CO transfer coefficient (KCO) |
| Type of pulmonary emphysema | At inclusion, every year, up to 5 years after surgery | Assessed by computed tomography scan : \[centro-lobular or pan-lobular, para-septal\] |
Countries
France
Contacts
Primary ContactJUNG Camille, MD
Outcome results
None listed